title: Genetic and biochemical determinants of serum concentrations of monocyte chemoattractant protein-1, a potential neural tube defect risk factor.
abstract: BACKGROUND
  Women with the AA genotype at the (-2518)A>G promoter polymorphism of CCL-2, which encodes the potent pro-inflammatory chemokine monocyte chemoattractant protein 1 (MCP-1), may be at increased risk for having offspring affected by spina bifida. As the A allele at this locus has been associated with decreased transcription of MCP-1 mRNA relative to the G allele, the observed genetic association suggests that the risk of spina bifida may be increased in the offspring of women with low MCP-1 levels. The present study was undertaken to identify potential determinants of MCP-1 levels in women of reproductive age.
  
  
  METHODS
  A small cohort of Caucasian and African-American women of reproductive age was recruited to participate in an exploratory investigation of the determinants of several disease-related, biochemical phenotypes, including MCP-1. Subjects completed a brief questionnaire and provided a fasting blood sample for biochemical and genetic studies. Potential biochemical, genetic, and lifestyle factors were assessed for their association with MCP-1 levels using linear regression analyses.
  
  
  RESULTS
  In this cohort, MCP-1 levels were significantly higher in Caucasians as compared to African-Americans. Further, among women of both races, there was evidence that MCP-1 levels were associated with smoking status, MTHFR 677C>T genotype, and red blood cell tetrahydrofolate levels.
  
  
  CONCLUSIONS
  The results of these analyses indicate that, if maternal CCL-2 genotype is related to the risk of spina bifida, this relationship is likely to be more complex than initially hypothesized, perhaps depending upon folate intake, MTHFR 677C>T genotype, the distribution of folate derivatives, and immune/inflammatory activity.
authors.affiliation: Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Lu
authors.forename: Megan
authors.initials: M
authors.lastname: Morales
authors.forename: Stephanie
authors.initials: S
authors.lastname: Khartulyari
authors.forename: Minghua
authors.initials: M
authors.lastname: Mei
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Anna
authors.initials: A
authors.lastname: Stanislawska-Sachadyn
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Summers
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Huang
authors.forename: Joan M
authors.initials: JM
authors.lastname: Von Feldt
authors.forename: Ian A
authors.initials: IA
authors.lastname: Blair
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mitchell
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Whitehead
mesh_terms: D000328:Adult; D001741:Black or African American; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D009436:Neural Tube Defects / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D044465:White People
chemical_list: D018932:Chemokine CCL2; D042965:Methylenetetrahydrofolate Reductase (NADPH2)